Convenient polymer-supported synthetic route to heterobifunctional polyethylene glycols

Conventional synthesis of heterobifunctional poly(ethylene glycol) derivatives, especially of medium size, is a rather tedious task. A straightforward solid-phase methodology has been developed that is illustrated here by the synthesis of alpha-pyridyldithio-omega-hydroxy-poly(ethylene glycol)(600). This derivative was prepared from resin-bound PEG(600) with a global yield of 65% for 6 individual steps, i.e., with an average yield of 93%/step. Intermediate purification steps simply consisted of resin washing. Progress of each reaction toward completion could conveniently Ire monitored by C-13 NMR of the resin-bound PEG derivatives. This example highlights both the versatility and efficiency of combining polymer-supported synthesis with direct C-13-NMR characterization of the intermediate compounds.